title: B cell activating factor inhibition impairs bacterial immunity by reducing T cell-independent IgM secretion.
abstract: B cell activating factor of the tumor necrosis factor family (BAFF) is an essential survival factor for B cells and has been shown to regulate T cell-independent (TI) IgM production. During Ehrlichia muris infection, TI IgM secretion in the spleen was BAFF dependent, and antibody-mediated BAFF neutralization led to an impairment of IgM-mediated host defense. The failure of TI plasmablasts to secrete IgM was not a consequence of alterations in their generation, survival, or early differentiation, since all occurred normally in infected mice following BAFF neutralization. Gene expression characteristic of plasma cell differentiation was also unaffected by BAFF neutralization in vivo, and except for CD138, plasmablast cell surface marker expression was unaffected. IgM was produced, since it was detected intracellularly, and impaired secretion was not due to a failure to express the IgM secretory exon. Addition of BAFF to plasmablasts in vitro rescued IgM secretion, suggesting that BAFF signaling can directly regulate secretory processes. Our findings indicate that BAFF signaling can modulate TI host defense by acting at a late stage in B cell differentiation, via its regulation of terminal plasmablast differentiation and/or IgM secretion.
authors.affiliation: Department of Biomedical Sciences, University at Albany, Albany, New York, USA.
authors.forename: Derek D
authors.initials: DD
authors.lastname: Jones
authors.forename: Maura
authors.initials: M
authors.lastname: Jones
authors.forename: Gregory A
authors.initials: GA
authors.lastname: DeIulio
authors.forename: Rachael
authors.initials: R
authors.lastname: Racine
authors.forename: Katherine C
authors.initials: KC
authors.lastname: MacNamara
authors.forename: Gary M
authors.initials: GM
authors.lastname: Winslow
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D004536:Ehrlichia / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D053668:Syndecan-1 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; D007075:Immunoglobulin M; D053668:Syndecan-1; C505720:Tnfsf13b protein, mouse